The TNF-α rs361525 and IFN-γ rs2430561 polymorphisms are associated with liver cirrhosis risk: a comprehensive meta-analysis

Front Immunol. 2023 Apr 14:14:1129767. doi: 10.3389/fimmu.2023.1129767. eCollection 2023.

Abstract

Background: Inflammation serves as an essential driver of liver cirrhosis (LC) incidence. Accordingly, a meta-analysis was carried out to explore the association between specific polymorphisms in the interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) genes and the incidence of LC based on comparisons of genotype and allele frequencies.

Objectives: To study the relationship between TNF-α rs361525 and IFN-γ rs2430561 polymorphisms and the risk of LC.

Methods: A database search was performed for all studies published as of September 10, 2022. The strength of risk relationships was assessed based on odds ratios (ORs) with 95% confidence intervals (CIs).

Results: Pooled analyses were conducted for one common TNF-α polymorphism (rs361525) as well as one common IFN-γ polymorphism (rs2430561). Both of these SNPs were identified as LC-related risk factors. Specifically, rs361525 was related to LC incidence in both alcoholic liver cirrhosis (OR: 1.86, 95%CI: 1.03-3.34) and hepatitis B virus (HBV)-related cirrhosis cases (OR: 1.44, 95%CI: 1.00-2.06) when using an allelic contrast model. Moreover, rs2430561 was significantly related to LC in an Asian population (OR: 1.45, 95%CI: 1.13-1.86) and in the context of HBV-related cirrhosis (OR: 1.48, 95%CI: 1.13-1.93) when using an allelic contrast model.

Conclusion: These findings indicate that rs361525 and rs2430561 represent LC-related risk factors, although additional large-scale clinical and case-control studies will be vital to confirm these results.

Keywords: interferon-γ; liver cirrhosis; metaanalysis; polymorphism; risk; tumor necrosis factor-α.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Fibrosis
  • Genetic Predisposition to Disease
  • Hepatitis B virus
  • Humans
  • Interferon-gamma* / genetics
  • Liver Cirrhosis* / genetics
  • Polymorphism, Single Nucleotide
  • Tumor Necrosis Factor-alpha* / genetics

Substances

  • Interferon-gamma
  • Tumor Necrosis Factor-alpha
  • IFNG protein, human
  • TNF protein, human

Grants and funding

This work was supported by Guangdong Basic and Applied Basic Research Foundation, China (2023A1515012422, 2019A1515011646), National Natural Science Foundation of China (81401689), Guangzhou Science and Technology Plan Project (202102080298) and Yat-sen Sailing Research Funds of Sun Yatsen Memorial Hospital of Sun Yat-sen University, China (YXQH202004).